25 Conclusion

We all know the statistics on the impact that breast cancer has on our population. Today, 1 in 8 women will experience breast cancer in her lifetime, and 1 in 33 women will die of the disease. In addition, in the United States, approximately 2000 men are diagnosed with breast cancer annually. Even more profound is the increase in the number of women living with breast cancer. Currently more than 2 million women in the United States have been successfully treated for breast cancer and are going on to live full and active lives subsequent to their treatment.¹ This statistic represents the tremendous impact that public awareness and education, early detection and diagnosis, and research into improved therapies can have on decreasing the burden of disease and improving quality of life. The impact that grassroots organizations and patient advocacy have had on increasing awareness and directing funding to important research initiatives serves as a model for those wishing to make a similar impact on other diseases that negatively affect the public good.

The importance and impact of well-conducted research trials are seen throughout the chapters of this book. Clinical trials conducted regarding prevention, imaging and early detection, local and systemic therapies, and quality of life have defined and redefined optimal care for patients and providers grappling with this disease. Funding for these clinical trials comes from many sources, including government funding agencies and private foundations. Recent financial reports indicate that annually the National Cancer Institute (NCI) sponsors $573 million in breast cancer research funding, the Department of Defense $138 million,² the Komen Foundation $64 million,³ and the Avon Foundation $14 million.⁴ Many other organizations large and small provide direct and indirect support for breast cancer research as well as additional monies to support education, public awareness, and direct patient care services. A significant portion of these funds comes from the generous donations of private citizens, many of whom have had personal experience with breast cancer and who want to do their part to help others in their community who have been touched by this disease.

The results of these clinical trials have moved breast cancer treatment from the early 1900s, when most patients received a Halsted radical mastectomy for local control, to this century, when many women can preserve their breast with minimal cosmetic change. This has come not at the detriment of survival but with improved survival rates. Most women diagnosed today can expect a greater than 70% 10-year survival rate; for those with the earliest stages of even invasive disease, a 10-year survival rate of over 90% is the norm. Surgeons have a wide armamentarium of options available to provide optimal local control as well as cosmetic outcome. Larger tumors can be converted to smaller tumors amenable to breast conservation with neoadjuvant chemotherapy. Oncoplastic techniques can reshape the breast to improve overall cosmesis in the breast conservation setting. Patients who require or choose mastectomy have a variety of reconstructive options available that can recreate the breast mound in a fashion that offers a very similar size, shape, and texture to the native breast. The future may bring ever more focal destruction and ablation techniques that will further minimize the cosmetic consequences of surgical breast cancer therapy.

As large debilitating surgical procedures have given way to smaller operations, further research has also better defined chemotherapy regimens in a similar vein. Although 40 years ago only one or two chemotherapy regimens were applied to all cases of breast cancer, the focus now is on the patients who are most likely to benefit from a given regimen while minimizing the side effects of these therapies. Substratification of tumor types by molecular characteristics has expanded breast cancer from being defined as one disease to recognizing distinct subsets with individual prognostic and treatment response signatures. Pregnancy-associated breast cancer, luminal or basal-subtype tumors, HER2/neu-positive tumors, triple-negative tumors, and tumors with low oncotype scores are currently recognized as having very distinct behaviors, and specific therapies are being developed to take these variations into consideration for treatment planning. Tailoring therapy to these specific subsets maximizes treatment benefit and further improves the cost-benefit ratio not only in financial terms but also in terms of the mental, physical, emotional, and relationship costs to the patient.

Similarly, radiation therapy is moving from a prolonged course of daily radiation to much shorter, more focused treatment modalities. Six-week courses of external-beam radiation therapy are being replaced with 3- to 4-week courses, brachytherapy radiation is being investigated for an even shorter on-treatment time, and some institutions are investigating single-dose, intraoperative treatment regimens. It is important to recognize, however, that intriguing and novel treatment options can often become available to the general public in advance of the data supporting equivalence or superiority to standard protocols. The application of these new techniques “off-protocol” needs to be carefully considered to prevent the unintentional introduction of less effective therapies in the absence of compelling research results. Carefully conducted research trials are the foundation for a future that will continue to focus on ever more targeted therapies to increase benefit and decrease morbidity.

As the medical management of breast cancer as a disease has improved, the opportunity to focus on risk stratification, prevention, and lifestyle interventions that can impact and reduce the incidence of breast cancer is receiving more attention. Identifying the women at highest risk for developing breast cancer, even though they currently represent a smaller proportion of all patients affected by this disease, allows targeted intervention either to prevent breast cancer or to identify early the development of breast cancer. Women and men identified as carrying known gene defects such as BRCA1 and BRCA2 are at particularly high risk. Earlier and more intensive screening can detect disease at the earliest possible stage, or prophylactic surgery can significantly decrease disease occurrence. Although effective medical therapies for chemoprevention for patients with a known gene defect have not yet been identified, the future will undoubtedly bring focused medical interventions that will correct the underlying defect, returning these family members to a baseline risk profile.

Learning from the experience of these highest-risk individuals, however, will lead to further improvements in risk stratification that will help us define and focus interventions on the women most likely to be affected by breast cancer. Most women who develop breast cancer have no known identifiable risk factors. For these women we currently have a one-size-fits-all approach to screening and early detection. Whatever your response to the recently published U.S. Preventive Services Task Force (USPSTF) recommendations on mammographic screening,⁵ the clear message is that most women will never get breast cancer, and identifying the women with an elevated risk will increase the yield and decrease the economic and noneconomic costs of screening. Targets that show promise include proliferative and atypical changes identified on benign breast biopsy, the quantification of breast density, and the influence of lifestyle markers such as obesity and sedentary lifestyle on subsequent breast cancer development.

Further definition of women at risk allows us to institute specific interventions such as chemoprevention and nutritional and lifestyle changes on the women most likely to benefit. Current prevention recommendations have been arbitrarily set at a 1.67% 5-year risk calculated using the Gail model. More specific modeling constructs as well as tailored prevention strategies are needed. Underutilization of currently available chemoprevention indicates that the side-effect profile of future medications must be much smaller than that demonstrated by tamoxifen and raloxifene if women are going to adopt them as part of their prevention strategy. Additional emerging strategies that include exercise and weight control also show promise as providing some reduction in breast cancer incidence, although they face the uphill battle of any intervention that requires significant behavior modification.

Efforts at early diagnosis rely heavily on imaging. Mammography continues to be the gold standard; however, emerging technologies such as magnetic resonance imaging (MRI) and whole-breast ultrasound appear to have important roles to play in a selected high-risk population. The importance of a clinical breast exam is often overlooked but needs to be reinforced because over one third of new breast cancers are diagnosed by the patient’s physician on physical exam. Use of image-guided and percutaneous biopsy techniques have tremendously improved the diagnostic quality while decreasing the cost of therapy. Percutaneous image-guided biopsy is becoming a quality measure for centers of excellence in breast disease management.

Imaging is also heavily used in the post-treatment surveillance setting. Again, adherence to established surveillance guidelines provides the optimal care. The importance of the physician, trained in comprehensive history and physical examination skills, cannot be overstated. Overutilization of surveillance imaging and laboratory testing is more likely to yield a false-positive than a true finding, increasing the burden of the emotional as well as the financial cost of care on the individual as well as the community.

As we better understand that breast cancer is not one disease but reflects many types of genetic alteration and phenotypic expression with variable aggression and prognosis, our prevention strategies and treatment therapies will be further honed and targeted to interventions appropriate to the disease process. This is an exciting time for a physician to participate in the care of these wonderful patients. The future holds promise of improved methods of diagnosis, more focused treatment, and improved survival and quality of life.

References

1 NCI Office of Women’s Health Research on Cancers in Women. http://women.cancer.gov/research/breast.shtml.

2 Priority #2: $150 million for the Department of Defense (DOD) Peer-Reviewed Breast Cancer Research Program (BCRP) for Fiscal Year 2009. National Breast Cancer Coalition. www.stopbreastcancer.org/index.php?option=com_content&task=view&id=333.

3 Komen Foundation Annual Report 2006–07. ww5.komen.org/uploadedFiles/Content_Binaries/Komen-AR2007.pdf.

4 Avon Foundation 2007 Financial Report. www.avoncompany.com/women/avonfoundation/2007_grants.pdf.

5 Screening for Breast Cancer. United States Preventive Services Task Force, Agency for Health Research and Quality. www.ahrq.gov/clinic/USpstf/uspsbrca.htm#summary. published November 19, 2009. Accessed February 20, 2010.

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